Beta-phenyl-gamma-nitroaldehydes



Patented Feb. 17, 1953 BETA-PHENYL-GAMMA-NITROALDEHYDES Owen A. Moe andDonald T. Warner, Minneapolis,

Minn., assignors to General Mills, Inc., a corporation of Delaware NoDrawing. Application February 18, 1949, Serial No. 7 7,283

9 Claims.

The present invention relates to novel gammanitrobutyraldehydes havingthe following formula:

HCgH

in which R and R are selected from the group consisting of hydrogen andlow alkyl groups.

The products of the present invention are, in general, oily liquids. Inview of the presence of the reactive nitro group and the aldehyde group,these compounds are particularly useful in organic synthesis, such asthe synthesis of amino acids, amino alcohols, substituted indolederivatives, and the like, as will be shown more fully hereinafter.

' It is therefore an object of the present invention to provide novelaldehyde compounds having the above formula.

It isa further object of the present invention to provide a novelprocess of preparing such compounds.

According to the present invention it has been found that variousaliphatic nitro compounds react with cinnamyl aldehyde to effect 1,4addition thereof to yield the corresponding gamma-nitrobutyraldehydes.These reactions are carried out in the presence of an alkaline catalystsuch as an alkali metal alkoxide, or in the presence of certain basicmaterials such as tertiary amines, for example, tributylamine. With thealkali metal alkoxide catalyst, the amount of catalyst is .as criticaland it is possible to use much larger quantities of catalyst up toequimolar proportions. The reaction'is carried out in the presence of asuitable solvent diluent which does not enter into the reaction. Almostany solvent diluent which meets this test may be employed. Suitablesolvents include alcohols such as ethanol, ethers such as diethyl ether,and hydrocarbon solvents such as benzene. The amount of solvent employedmay be variedconsiderably. Usually it is 2 desired to employ a quantityof solvent at leas equal to the volume of the ester employed. Ingeneral, the larger the quantity of solvent, the easier it is to controlthe reaction in the desired direction. It is apparent that the quantityof solvent employed is limited by the problem of recovering the solvent.

The temperature employed during the addition reaction is subject toconsiderable change. Usually a temperature within the rang of 0-50 C. isdesirable. At temperatures above 50 C.there is some possibility of sidereactions.

In carryin out the reaction it is preferred to prepare a solution of thenitro paraffin in the solvent and to add the catalyst to this solution.The resultant solution is then cooled to a suitable temperature forreaction and the unsaturated aldehyde is added slowly to the solutionover an extended period of time. In this way it is possible to controlthe temperature of the reaction mixture very readily to within thedesired range, and thus to control the reaction in the desireddirection. After the reaction has been completed, the catalyst may beneutralized and the product worked up in a conventional manner.

While the specific examples herein described are with particularreference to l-nitropropane and Z-nitropropane, it is understood thatother nitro compounds such as nitromethane, nitroethane, andnitrobutane, may be used. In general, nitro paraffins which producecompounds having the general formula given herein in which R and R arelow alkyl groups containing from one to four carbon atoms, may be used.

The following examples iwill serve todllustrate the invention: .1 g

. Example 1 Absolute ethanol ml.) was reacted with 0.1 g. of sodium andthe resulting sodium ethoxide solution was mixed with 22.3 g. ofZ-nitropropane. The reaction mixture (at 25 C.) was treated withcinnamyl aldehyde (33 g.) and the resulting solu tion was allowed tostand for 16 hours at room temperature. The catalyst was thenneutralized by the addition of 0.8 g. of glacial acetic acid and theneutralized solution was concentrated in vacuo to yieldgamma-nitro-gamma-methylbeta-phenylpentanal as a residual oil. Thisresidual oil was dissolved in benzene (200 ml.) and washed with four 50ml. portions of water. The benzene layer was dried over anhydrous sodiumsulfate and after removal of the benzene by vacuum distillation, theresidual oil was distilled. The product was collected in two fractionsboiling at 118-128 C. (0.26 mm.) n =1.5310, and 128- d'rous sodiumsulfate.

' 135-182 C. (0.3-0.8 mm.).

138 C. (0.26 mm.) n =1.5298. The two fractions were then recombined andsubjected to an additional distillation. The purified material boiled at1l1.5-112.5 C. (0.2 mm.) n =1.5299. A portion of the redistilled productwas treated with 2,4-dinitrophenylhydrazine in a conventional manner,and the 2,4-dinitrophenylhydrazone of gamma-nitro-gamma-methyl-beta-phenylpentanal was obtained as a crystalline product melting at 181-182 C.

Example 2 Absolute ethanol (75 ml.) was reacted with 0.06 g. of sodiumand the resulting sodium ethoxide solution was mixed with 22.3 g. of 1-nitropropane. This reaction mixture at a temperature of 26 C., wastreated with 30.5 g. of cinnamyl aldehyde and the reaction temperaturewas observed to increase to 40 C. over a 15- minute period. The reactionwas allowed to proseed for an additional 1% hours and the catalystfraction was treated with 2,4-dinitrophenylhy drazine in the usualmanner and the 2,4-dinitrophenylhydrazone ofgamma-nitro-beta-phenylhexanal melted at 204-2045 C. dec. afterrecrystallization from an ethanol-ethyl acetate solvent mixture.

Compounds of the type disclosed in the present invention may beconverted into new and novel indole derivatives as shown below:

CHaOHzCHNOa C6115 CHCBHS CHCHNOz I J CH2 The nitrobutyraldehydes may beemployed in the synthesis of new hydan-toins in the following manner:

CH2-C -GHa OHCeHs CHO The synthesis of interesting organic intermediatesmay be accomplished by the simul taneous condensation-reduction of thealdehyde compound with ethyl cyanoacetate:

No, (3E1 CH3- CH3 CHaC-CH3 Ce s HCaHs H5 H2 ON L o LHZCH COOEtConversion of the carbonyl group to the carboxyl group and conversion ofthe nitro group to an amino group results in new and interesting aminoacids:

CHBCHzCHNOz IHCoHa CH2 I CHO CHBCHQCHNOi HC H5 OOH CHzCHzCHNH:

HCaH;

Amino alcohols may be produced by reduction of the carbonyl, and thenitro groups as indicated in the following reaction:

N02 NH? CHa-C-CH3 CHz--CH: ($110,11 011cm,

Hz H: CH0 (JHzOH While various modifications of the invention have beendescribed, it is to be understood that the invention is not limitedthereto, but that other variations are possible without departing fromthe spirit thereof.

We claim as out invention:

1.Nitroaldehydes having the following for mula: I

N02 Rat-Ra H2 tea in which R and R are selected from the groupconsisting of hydrogen and low alkyl groups.

2. Nitroaldehydes having the following formula:

N02 R1(|3R1 HC1H5 2H: (mo

in which R and R are low alkyl groups.

3. Nitroaldehydes having the following for-- mula:

$02 H-o-R 0110611; F CHO in which R is a low alkyl group.

Beta-phenyl-gamma-nitrohexanal. 5. Beta-phenyl-gamma-nitro-gamma methyl-Dentanal.

6. Process of producing aldehyde compounds having the following formula:

in which R and R are selected from the group consisting of hydrogen andlow alkyl groups, which comprises reacting cinnamyl aldehyde with a,substantially equi-molecular quantity of a nitro paraffin having theformula CHNO:

in the presence of an alkaline catalyst.

7. Process of preparing nitroaldehydes having the following formula:

1T0: IU-C-R" JHCeHI in which R and R. are selected from the groupconsisting of hydrogen and low alkyl groups, which comprises preparing asolution of a substantially equi-molecular quantity of a nitro paraffinhaving the following formula CHNO1 in an inert solvent together with analkaline catalyst, gradually adding cinnamy1 aldehyde thereto, andmaintaining the temperature of the reaction mixture not substantially inexcess of 50 C.

8. Process of preparing beta-phenyl-gammamethyl gamma nitropentanalwhich comprises REFERENCES CITED The following references are of recordin the file of this patent:

UNITED STATES PATENTS Number Name Date 2,332,482 Degering et a1 Oct. 19,1943 2,355,402 Sussman Aug. 8, 1944 2,475,996 Smith July 12, 1949 OTHERREFERENCES Kohler: J. A. C. 5., vol. 38, pages 889-900 (1916).

Hass et al.: Chem. Rev. (3), vol. 32, pages 416 and. 417 (1943).

Fort et al.: J. Chem. Soc. (London), 1948, pages 1907-19,

1. NITROALDEHYDES HAVING THE FOLLOWING FORMULA;